Herman F Wunderink1, Caroline S de Brouwer2, Els van der Meijden2, Diana V Pastrana3, Aloysius C M Kroes2, Christopher B Buck3, Mariet C W Feltkamp2. 1. Department of Medical Microbiology, Leiden University Medical Center, Leiden, the Netherlands. Electronic address: H.F.Wunderink@umcutrecht.nl. 2. Department of Medical Microbiology, Leiden University Medical Center, Leiden, the Netherlands. 3. Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20892-4263, USA.
Abstract
BACKGROUND: The BK polyomavirus (BKPyV) is subdivided into four genotypes. The consequences of each genotype and of donor-recipient genotype (mis)match for BKPyV-associated nephropathy (BKPyVAN) in kidney transplant recipients (KTRs) are unknown. OBJECTIVES: To develop and evaluate a genotype-specific IgG antibody-based BKPyV serotyping assay, in order to classify kidney transplant donors and recipients accordingly. STUDY DESIGN: VP1 antigens of six BKPyV variants (Ib1, Ib2, Ic, II, III and IV) were expressed as recombinant glutathione-s-transferase-fusion proteins and coupled to fluorescent Luminex beads. Sera from 87 healthy blood donors and 39 KTRs were used to analyze seroreactivity and serospecificity against the different BKPyV genotypes. Six sera with marked BKPyV serotype profiles were analyzed further for genotype-specific BKPyV pseudovirus neutralizing capacity. RESULTS: Seroreactivity was observed against all genotypes, with seropositivity rates above 77% comparable for KTRs and blood donors. Strong cross-reactivity (r > 0.8) was observed among genotype I subtypes, and among genotypes II, III and IV. Seroresponses against genotypes I and IV seemed genuine, while those against II and III could be out(cross)competed. GMT (Luminex) and IC50 (neutralization assay) values showed good agreement in determining the genotype with the strongest seroresponse within an individual. CONCLUSIONS: Despite some degree of cross-reactivity, this serotyping assay seems a useful tool to identify the main infecting BKPyV genotype within a given individual. This information, which cannot be obtained otherwise from nonviremic/nonviruric individuals, could provide valuable information regarding the prevalent BKPyV genotype in kidney donors and recipients and warrants further study.
BACKGROUND: The BK polyomavirus (BKPyV) is subdivided into four genotypes. The consequences of each genotype and of donor-recipient genotype (mis)match for BKPyV-associated nephropathy (BKPyVAN) in kidney transplant recipients (KTRs) are unknown. OBJECTIVES: To develop and evaluate a genotype-specific IgG antibody-based BKPyV serotyping assay, in order to classify kidney transplant donors and recipients accordingly. STUDY DESIGN:VP1 antigens of six BKPyV variants (Ib1, Ib2, Ic, II, III and IV) were expressed as recombinant glutathione-s-transferase-fusion proteins and coupled to fluorescent Luminex beads. Sera from 87 healthy blood donors and 39 KTRs were used to analyze seroreactivity and serospecificity against the different BKPyV genotypes. Six sera with marked BKPyV serotype profiles were analyzed further for genotype-specific BKPyV pseudovirus neutralizing capacity. RESULTS: Seroreactivity was observed against all genotypes, with seropositivity rates above 77% comparable for KTRs and blood donors. Strong cross-reactivity (r > 0.8) was observed among genotype I subtypes, and among genotypes II, III and IV. Seroresponses against genotypes I and IV seemed genuine, while those against II and III could be out(cross)competed. GMT (Luminex) and IC50 (neutralization assay) values showed good agreement in determining the genotype with the strongest seroresponse within an individual. CONCLUSIONS: Despite some degree of cross-reactivity, this serotyping assay seems a useful tool to identify the main infecting BKPyV genotype within a given individual. This information, which cannot be obtained otherwise from nonviremic/nonviruric individuals, could provide valuable information regarding the prevalent BKPyV genotype in kidney donors and recipients and warrants further study.
Authors: F K Baksh; S D Finkelstein; P A Swalsky; G L Stoner; C F Ryschkewitsch; P Randhawa Journal: Am J Kidney Dis Date: 2001-08 Impact factor: 8.860
Authors: H F Wunderink; E van der Meijden; C S van der Blij-de Brouwer; M J K Mallat; G W Haasnoot; E W van Zwet; E C J Claas; J W de Fijter; A C M Kroes; F Arnold; A Touzé; F H J Claas; J I Rotmans; M C W Feltkamp Journal: Am J Transplant Date: 2016-07-08 Impact factor: 8.086
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Authors: Diana V Pastrana; Upasana Ray; Thomas G Magaldi; Rachel M Schowalter; Nicolas Çuburu; Christopher B Buck Journal: J Virol Date: 2013-07-10 Impact factor: 5.103
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Authors: H F Wunderink; C S De Brouwer; L Gard; J W De Fijter; A C M Kroes; J I Rotmans; M C W Feltkamp Journal: Open Forum Infect Dis Date: 2019-02-19 Impact factor: 3.835
Authors: Martina Saláková; Viera Ludvíková; Eva Hamšíková; Marie Kolářová; Vojtěch Šroller; Ondřej Viklický; Mariana Wohlfahrtová Journal: Front Immunol Date: 2022-07-25 Impact factor: 8.786